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From 2012 to 2017, many adverse events, such as irregular vaginal bleeding and menstrual disorders, associated with the use of health foods containing Pueraria mirifica were reported in PIO-NET. Health foods containing P. mirifica claim mastogenic or body shaping effects, and it is for this reason that many women use these products. As a result, the Japanese government investigated and assessed the possibility of the occurrence of adverse effects associated with the use of other ingredients in health foods and labelled P. mirifica, Coleus forskohlii, black cohosh, and greater celandine as "designated ingredient, etc."The present study showed that recognition of "designated ingredient, etc." was 45.9% and that there was a difference between consumers and healthcare professionals. The prevalence of food containing P. mirifica use was 1.2%. Almost half of users experienced adverse events, such as irregular vaginal bleeding and menstrual disorder. Some subjects had a good perception towards "designated ingredient, etc.," such as "It seems effective"(32.7%) and "It seems good for health"(18.9%). After reading the descriptive text, their positive perceptions decreased.In conclusion, the recognition of "designated ingredient, etc." is insufficient. To avoid adverse events associated with "food containing designated ingredient, etc.," detailed information should be provided.

Obesity is one of the main causes of non-alcoholic steatohepatitis (NASH), which is associated with impaired liver functions including drug metabolism. Coleus forskohlii extract (CFE) is a popular ingredient of weight loss dietary supplements in Japan. In this study, we examined the effect of CFE on the treatment of NASH. C57BL/6 mice (male, 10-wk-old) were fed a NASH diet (high-fat, low-methionine, and choline-deficient diet) for 12 wk to establish NASH. Then, we examined the effect of 0.5% (w/w) CFE in diet during diet-treatment (change to control diet) and/or treadmill-exercise (45 min at 20 m/min, 5 d/wk) to improve NASH for 3 wk. After experimental period, lipids profiles and liver functional markers in the blood, and hepatic lipid content and major CYP subtype mRNA expression and activity in liver were measured. Diet-treatment, but not exercise decreased liver weight and hepatic lipid contents in NASH induced mice. CFE attenuated the effects of diet-treatment which reduced liver weight, even though body weight and adipose tissue weight were reduced. Further, CFE significantly increased liver microsomal CYP1A1, CYP1A2, CYP2C, and CYP3A activities in each condition, and CYP inductions were greater in diet-treatment group compared to those in exercise group. These results suggest that taking CFE should be avoided during diet-treatment of NASH, especially in patients under medication.

We examined CYP induction and recovery at various doses of Coleus forskohlii extract (CFE) to assess potential drug interactions by a mechanism involving intestinal CYP. Mice were administered diets with various doses of CFE up to 0.5% (equivalent to 700-800 mg/kg body weight) for 2 weeks, then CFE was withdrawn for 3 d. Changes in CYP activities and mRNA expression in the small intestine and liver were then evaluated. CFE induced CYP in the small intestine at a higher dose compared to the liver; CYP3A was induced at 0.5% and 0.005% CFE in the small intestine and liver, respectively. There was no sex difference in CFE dose for CYP induction. CYP induction quickly reverted after withdrawal of CFE, especially for CYP3A, in the small intestine; whereas, a gradual recovery was observed in the liver. In conclusion, CFE induced CYP in the small intestine and liver; however, a higher dose of CFE was needed for the small intestine. Moreover, the induction was soon recovered, suggesting actual interactions of CFE with prescription drugs are unlikely to occur through CYP in the small intestine.

Coleus forskohlii extract (CFE), a popular weight-loss herbal product, induces hepatic cytochrome P450 (CYP) and fatty liver in mice; however, its main bioactive ingredient, forskolin, does not show such effects. To ensure the safety of CFE as a dietary supplement, identification of the compounds implicated in the induction of hepatic CYP and fatty liver is required. In this study, we separated a crude CFE extract into 5 fractions (Fr.) by column chromatography and administered the fractions to mice for one week to assess their ability to induce CYP and fatty liver. CYP induction was detected for all fractions, indicating that many compounds may be involved in CYP induction, while fatty liver was only detected for Fr. 2. Further isolation and purification of Fr. 2 by column chromatography identified 14-deoxycoleon U as a major compound and crocetin dialdehyde as a pigment compound. An in vivo mouse study revealed that crocetin dialdehyde had no effect on the liver and, as 14-deoxycoleon U was the major compound in Fr. 2, it is likely that the active compound inducing fatty liver in CFE is 14-deoxycoleon U. These findings will facilitate the preparation of standardized safe CFE ingredients for dietary supplements.

This paper deals with proficiency testing schemes for food nutrition analysis in Japan. In schemes in 2017 and 2018, 65 and 73 organizations participated, respectively, and more than 70% of the participants were public organizations responsible for a nutrition-labeling compliance test. The food matrices were pork and chicken sausages, and analytes were protein, fat, ash, moisture, carbohydrate, energy, sodium, salt equivalent, calcium (2018 only), and iron (2018 only). The organizations reporting inadequate laboratory values in one or more nutrients for mandatory declaration (energy, protein, fat, carbohydrate, or salt equivalent) were 11 and 15% of all organizations and 9 and 13% of public organizations in the 2017 and 2018 schemes, respectively. The approximate relative standard deviations for proficiency assessment (RSDr) were as follows: protein, 2%; fat, 3%; ash, 2%; moisture, 0.5%; carbohydrate, 9%; energy, 1%; sodium (salt equivalent), 4%; calcium, 7%; and iron, 7%. Notably, the large RSDr value for carbohydrate may cause inconsistency among laboratories in compliance tests for foods containing several grams or less of carbohydrate per 100 grams.

We examined CYP induction and recovery at various doses of Coleus forskohlii extract (CFE) to assess potential drug interactions by a mechanism involving intestinal CYP. Mice were administered diets with various doses of CFE up to 0.5% (equivalent to 700-800 mg/kg body weight) for 2 weeks, then CFE was withdrawn for 3 d. Changes in CYP activities and mRNA expression in the small intestine and liver were then evaluated. CFE induced CYP in the small intestine at a higher dose compared to the liver; CYP3A was induced at 0.5% and 0.005% CFE in the small intestine and liver, respectively. There was no sex difference in CFE dose for CYP induction. CYP induction quickly reverted after withdrawal of CFE, especially for CYP3A, in the small intestine; whereas, a gradual recovery was observed in the liver. In conclusion, CFE induced CYP in the small intestine and liver; however, a higher dose of CFE was needed for the small intestine. Moreover, the induction was soon recovered, suggesting actual interactions of CFE with prescription drugs are unlikely to occur through CYP in the small intestine.

The current adverse event reporting systems are inadequate to prevent potential health damage caused by dietary supplement use, and a better case-collecting system is needed. The aim of this study was to examine whether online surveys would be a useful methodology for estimating ongoing adverse events, focusing on diarrhea as a model symptom. We used four online survey companies and requested that they administer the same questionnaire to their registrants regarding experiences of adverse events associated with supplement use and details of diarrhea symptoms, as well as the product and ingredient names of suspected supplements. Of 78,220 dietary supplement users, 9% to 25% reported experiencing adverse events in the previous year. A total of 723 participants who answered affirmatively about a putative causal relationship between supplement use and the onset of diarrhea and who clearly identified the product and/or ingredient were eligible for final analysis. Comparisons among the survey companies showed differences in the proportions of reported symptoms; however, the rank orders were consistent in the preliminary survey. Also, when analysis was limited to specific participants from a full-scale survey, even the numerical values of the proportions were consistent among the four companies. Herbal/botanical ingredients, specifically Coleus forskohlii, were the ingredients most frequently reported to be associated with diarrhea. These results indicate that online survey can be a useful method to complement the current system for estimating ongoing adverse events and identifying the responsible supplements.

Vitamins are essential nutrients for human beings. Therefore, accurate determination of vitamin levels in foodstuffs is vital to confirm the proper intake of vitamins. The microbiological assay (MBA), which is used worldwide for the determination of several vitamins in foodstuffs, is very sensitive and can determine ng/mL levels of vitamins. However, the correlation between vitamin concentrations in a sample solution and the plotted growth is usually shown as a sigmoid curve. Therefore, a calibration curve derived from a linear regression may lead to error. In this study, we evaluated the effects of various models (linear, quadratic, and cubic regression models and a four-parameter logistic model (4PLM)) for calibration curve construction on the determination of vitamin B6 in infant formula. Among the four models, the calibration curve constructed with 4PLM was the most reliable for vitamin B6 determination. Moreover, the calibration curve based on 4PLM showed robustness for extrapolation; even if the vitamin concentration in the sample solution deviated from the range of the standard solution, a reasonable result could be obtained. Similarly, the 4PLM calibration curve was the most reliable for niacin determination. We conclude that 4PLM should be used for calibration curve construction to improve the reliability of vitamin determination in foodstuffs using MBA.

The current adverse event reporting system for dietary supplements lacks the ability to collect and analyze ongoing case reports in sufficient numbers to detect health issues. We conducted an online survey to collect data on skin manifestations due to supplement use in consumers and to identify the suspected products and ingredients. An online survey was conducted among 63,737 dietary supplement users in 2016. Those who self-reported experiences of skin anthema or itching caused by supplement use and recognized a causal relationship as almost certain (0.8%) were invited to provide further details of symptoms and products. Most of the users experienced mild symptoms with "itching and/or rash of body part." After the onset of skin manifestations, 69.3% ceased supplement use, while 26.6% continued supplement use, including those who reduced the amount or frequency of use. Respondents who visited the hospital in response to symptoms accounted for 26.0%, while 53.3% did not seek treatment. The products used were identified in 155 of 300 eligible respondents. Although those products were composed of multiple ingredients, the accumulated data suggested that cutaneous symptoms were related to the following constituents: "Peptides or animal by-products" (31.0%), "Herbal/Botanical" (23.2%) and "Fats and lipid" (13.5%). Conducting an online survey to elicit information directly from consumers identified components of supplements that are involved in skin manifestations that could lead to serious damage, and may fill a void in the current adverse event reporting system.

The interaction of levodopa and vitamin B6 is a well-known issue. This study investigated the incidence of unacceptable intake levels of vitamin B6 among levodopa users by means of a systematic review. We searched two databases (PubMed and "Igaku Chuo Zasshi") for articles about adverse events due to the interaction of levodopa and vitamin B6 published up to August 2017. Of 98 citations retrieved, 11 studies met the selection criteria. The results indicated that a vitamin B6 intake level of more than 50 mg/day could reduce the efficacy of levodopa. The recommended intake of vitamin B6 for Japanese adults is 1.4 mg/day for men and 1.2 mg/day for women. Therefore, the acceptable intake of vitamin B6 for levodopa patients would be within the range of the recommended intake level, which is also within the usual range in foods in Japan, except for dietary supplements or health foods. Levodopa users should be cautious about taking dietary supplements and over-the-counter drugs.

Cancer patients use health foods (HFs) as complementary and alternative medicine, although the details of their adverse events (AEs) are unclear. We searched three databases [PubMed, "Igaku Chuo Zasshi", and Information System on Safety and Effectiveness for Health Foods website (https://hfnet.nibiohn.go.jp/)] for case reports on AEs related to HF intake in cancer patients published before October 2018. Of the matched reports, 76 studies and 92 patients (31 in Japan, 61 overseas) that met the selection criteria were included in this review. Thus, the severity of AEs and outcomes were not related to either the concomitant use of HF with cancer chemotherapy or cancer stages of patients. AEs caused by HF intake itself accounted for 87%, while drug-HF interaction accounted for 11%. According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, 70% of patients whose grades were identified had severe cases (grades 3 to 5). In Japanese patients, hepatic and respiratory disorders accounted for 52% of the severe cases. Cases were predominantly developed as a result of an allergic mechanism, and mushroom products were mostly used. Overseas, serious cases were induced by products that were already indicated for safety problems. Moreover, notable AEs were recognized, such as hypercalcemia, which were caused by intake of HF containing calcium, vitamin D, and shark cartilage, and bacterial infection caused by probiotic products. Analyzing the details of AEs related to HF intake can help health professionals and cancer patients prevent health hazards.

Coleus forskohlii extract (CFE), a popular weight-loss herbal product, induces hepatic cytochrome P450 (CYP) and fatty liver in mice; however, its main bioactive ingredient, forskolin, does not show such effects. To ensure the safety of CFE as a dietary supplement, identification of the compounds implicated in the induction of hepatic CYP and fatty liver is required. In this study, we separated a crude CFE extract into 5 fractions (Fr.) by column chromatography and administered the fractions to mice for one week to assess their ability to induce CYP and fatty liver. CYP induction was detected for all fractions, indicating that many compounds may be involved in CYP induction, while fatty liver was only detected for Fr. 2. Further isolation and purification of Fr. 2 by column chromatography identified 14-deoxycoleon U as a major compound and crocetin dialdehyde as a pigment compound. An in vivo mouse study revealed that crocetin dialdehyde had no effect on the liver and, as 14-deoxycoleon U was the major compound in Fr. 2, it is likely that the active compound inducing fatty liver in CFE is 14-deoxycoleon U. These findings will facilitate the preparation of standardized safe CFE ingredients for dietary supplements.

In HPLC analyses of soluble dietary fiber, desalting processes using open, mixed-bed ion-exchange columns are time-consuming and labor-intensive. We developed and validated a simple desalting method using tandem cation/anion exchange SPE cartridges. We found that combining Bond Elut Jr SCX (upstream) and Bond Elut PSA (downstream) cartridges provided adequate desalting of test solutions. The developed method was then validated in an inter-laboratory study. Five test samples were prepared by mixing food matrixes with purified soluble dietary fiber and treated to generate solutions to test the desalting process. These solutions were then analyzed by eight different laboratories. The results demonstrated that the developed method is simple and reliable for desalting samples containing 140 to 945 mg/100 mL of soluble dietary fiber in preparation for HPLC analysis of soluble dietary fiber.

The formulations of the functional ingredients of dietary supplements was studied with a small number of subjects, with a particular focus on their effectiveness, but not enough to evaluate their safety. In this regard, the reevaluation and estimation of the safe use of marketed products, with regards to their adverse event (AE) frequencies, are important. To address this issue, a post-marketing nationwide online survey was conducted for the herbal ingredient Coleus forskohlii extract (CFE), a popular weight-loss ingredient. The questionnaire included product names, adherence to the claimed amount, and AE experiences. The safe intake amount was estimated by the relationship between the claimed amount of CFE and the frequencies of AEs of each product. The number of users who experienced AEs was 75 (10.5% of all users). Gastrointestinal symptoms accounted for 92.0% (n = 69) of all AEs, and diarrhea alone accounted for 81.3% (n = 61). The amount of CFE was significantly associated with the occurrence of diarrhea (p = 0.005). The fitted curve showed that the safe intake amount of CFE was less than 250 mg/day, however, considering its effectiveness, 500 mg/day of CFE might be acceptable. In conclusion, nationwide online surveys of users enable us to confirm and reevaluate the safety of herbal supplements.

Objectives Non-alcoholic fatty liver disease (NAFLD) is associated with impaired liver function, and resveratrol could suppress NAFLD progression. This study examined the effects of NAFLD on the expression of major cytochrome P450 (CYP) subtypes in the liver and whether the expression could be attenuated by resveratrol. Methods C57BL/6 mice (male, 10 weeks of age) were fed a high-fat and high-sucrose (HFHS) diet to induce NAFLD. Major Cyp subtype mRNA expression in the liver was measured by real-time RT-PCR. Key findings Body and liver weights at 4 and 12 weeks were significantly higher in mice fed the HFHS diet compared with control. The HFHS diet significantly increased the accumulation of cholesterol and triglycerides at 12 weeks. Under this condition, the HFHS diet increased the expression of Cyp1a2 and decreased that of Cyp3a11 at 1 week and thereafter. On the other hand, Cyp1a1, 2b10 and 2c29 mRNA expression levels in the liver were significantly increased at 12 weeks only. Resveratrol (0.05% (w/w) in diet) slightly suppressed lipid accumulation in the liver, but failed to recover impaired Cyp gene expression levels in NAFLD. Conclusions Drug metabolism may be impaired in NAFLD, and each Cyp subtype is regulated in a different manner.

Kazuki Ide,1 Hiroshi Yamada,1 Yohei Kawasaki,1 Marika Noguchi,1 Mamoru Kitagawa,1 Tsuyoshi Chiba,2 Yoshiyuki Kagawa,3 Keizo Umegaki2 1Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Information Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, 3Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan Background: Dietary supplements are used by >50% of the adult population in Japan, and adverse events related to these products have been reported with their increased use. Thus, an efficient system to gather and report data on these adverse events is essential. To date, however, reporting has been limited. The aim of this study was to address this deficiency by exploring the routine reporting practices of the medical staff employed at clinics or pharmacies in Japan.Methods: We conducted a survey of the procedures used by the medical staff to report adverse events related to dietary supplement intake to public health centers in Japan. The survey was conducted in Japan between November 2015 and January 2016. Based on a sample size calculation, questionnaires were administered to 1,700 potential respondents (850 pharmacists and 850 physicians). The questionnaire inquired about the sociodemographic characteristics and dietary supplement-related adverse event-reporting practices.Results: The response rate was 34.7%, including 286 pharmacists and 304 physicians. Although >30% of the pharmacists and physicians had prior experience dealing with such adverse events

This study was performed to reveal factors associated with dietary supplement use among Japanese preschool children in a nationwide survey. A cross-sectional, Internet survey was conducted among 2,058 mothers aged 20-40 y old who had preschool children and were registrants of a Japanese social research company in February 2013. The questionnaires assessed dietary supplement use, lifestyle and eating habits in both children and their mothers, eating awareness among mothers and the mothers' sources of health information. The study employed logistic regression analysis to evaluate the association between dietary supplement use and other variables. Dietary supplements were used by 8.0% of the children. Children who used supplements tended to be older in age, less likely to "get up cheerfully every morning," more likely to skip breakfast, eat out more frequently, and have mothers who used supplements, than children who did not use supplements. Mothers' level of education and household income were not associated with supplement use among their children. It is likely that mothers' anxiety about their children's health or unhealthy eating habits has a striking effect on supplement use among children. However, the actual dietary balance and daily rhythms of child supplement users were not irregular or unhealthy. It is necessary to give more accurate information on children's dietary habits and health to address mothers' anxiety.

Aim Resveratrol is a popular ingredient in dietary supplements. Some patients concomitantly use dietary supplements and medicines in Japan. In the present study, we determined whether trans-resveratrol and melinjo (Gnetum gnemon L.) seed extract (MSE), which contains resveratrol dimers, interacted with drugs using a mouse model. Methods Male C57BL/6J mice were fed experimental diets containing 0.005%, 0.05%, or 0.5% (w/w) trans-resveratrol or MSE for 1 or 12 weeks. The expression of liver cytochrome P-450 (CYP) mRNA and activity of liver microsomal CYP were measured. To determine the influence of resveratrol or MSE on drug efficacy, the anticoagulant activity of warfarin was examined in mice that were fed diets containing trans-resveratrol or MSE for 12 weeks. Results When the mice were fed experimental diets for 1 week, none of the doses of trans-resveratrol and MSE affected body weight, liver weight, or plasma AST and ALT levels. Trans-resveratrol also did not affect CYP1A1, CYP1A2, CYP2C, or CYP3A activities. In contrast, 0.5% MSE slightly increased CYP1A1 activity. When the mice were fed experimental diets for 12 weeks, 0.05% trans-resveratrol increased CYP1A1, CYP2C, and CYP3A activities, whereas 0.5% MSE suppressed CYP3A activity. Under these conditions, 0.5% trans-resveratrol enhanced the anticoagulant activity of warfarin, although CYP2C activity increased. However, MSE did not affect the anticoagulant activity of warfarin. Conclusion The 0.05% trans-resveratrol did not interact with warfarin in a mouse model, whereas 0.5% trans-resveratrol may have enhanced the anticoagulant activity of warfarin.

The prevalence of dietary supplement use, such as vitamins, minerals, or fish oil, has increased among children in Japan, however, whether children are using dietary supplements appropriately remains unclear. This study aimed to determine dietary supplement use among children. In August 2017, a nationwide internet preliminary survey of 265,629 mothers aged from 25 to 59 years old was undertaken. Of these, 19,041 mothers of children attending either elementary school, junior high school, or high school were selected. Among them, 16.4% were currently providing their children with dietary supplements and 5.2% had previously given dietary supplements to their children. The prevalence of dietary supplement use was higher in boys than in girls, and the prevalence increased according to their grade. A total of 2439 participants were eligible to undertake a targeted survey on dietary supplement use. Dietary supplements were being taken to maintain health, supplement nutrients, and enhance growth in both boys and girls, and many children (37.5%) were provided with vitamin and mineral supplements. Mothers mainly obtained information concerning dietary supplements via the internet, and supplements were purchased in drug stores or via the internet. The prevalence of dietary supplement use in mothers was 65.4% and may be associated with the prevalence rates in children. Some mothers reported adverse events (3.6%) in their children, such as stomachache, diarrhea, nausea and vomiting, and constipation. The cause-and-effect relationships for adverse events were not clear, but some children were given products for adults. Children are more influenced by dietary supplements compared to adults. To prevent adverse events due to inappropriate use, parental education concerning dietary supplements is essential.

Objectives The purpose of this study was to examine the relationship between dietary supplement use and personality traits among Japanese female students.Methods A cross-sectional questionnaire survey was administered to 230 female university or junior college students in October and November 2015; 228 students responded. The questionnaires inquired regarding the usage of dietary supplements and attitudes about dietary supplements, as well as the healthy eating literacy (HEL) scale and the Big Five personality traits. In total, 124 respondents completed the survey. The Mann-Whitney U test, Kruskal-Wallis test, chi-square test, and Spearman's correlation coefficient were used to examine dietary supplement-personality relationships.Results Overall, 19.4% of students reported using dietary supplements. Supplement users had high extraversion scores compared with non-users. Attitudes about dietary supplements and HEL were not associated with personality traits.Conclusion Personality traits influenced dietary supplement use, although limitedly.

The prevalence of dietary supplement use has increased in Japan, and consumers can purchase supplements from foreign countries through the internet. Therefore, it is important to consider both domestic and overseas safety alerts to prevent adverse events associated with dietary supplement use. We have been collecting global safety alerts associated with dietary supplements and providing this information to the public via the "Information system on safety and effectiveness for health foods (HFNet)" website. In this study, we analyzed the characteristics of safety alerts from 2010 to 2016 in HFNet (total: 2,124 alerts). The most common reason for alerts was illegal adulteration with pharmaceutical substances (85%), and sexual enhancement or weight loss products accounted for 68% of all alerts. Most alerts were based on market surveillance reports or recall information. However, 181 adverse event reports were identified, and most of them were related to weight loss or disease treatment in patients. In Japan, a majority of the adverse events was caused by products intended for weight loss or purchased online, and young female users were commonly involved. These findings should be helpful for prevention of adverse events associated with dietary supplement use.

To clarify the prevalence of dietary supplement use among college students, we conducted Internet-based nationwide questionnaire surveys with 157,595 Japanese college students aged between 18 to 24 years old who were registrants of Macromill Inc. (Tokyo, Japan). Among the 9066 respondents (response rate 5.8%), 16.8% were currently using dietary supplements. The prevalence of dietary supplement use did not differ significantly between males (17.1%) and females (16.7%). However, it increased according to their grade (13.1% to 20.5%), and it was higher in medical and pharmaceutical college students (22.0%) compared to others (16.7%). The main purpose of dietary supplement use was for the health benefits in both males and females. Other reasons were to build muscle in males, and as a beauty supplement and for weight loss in females. According to the purpose of dietary supplement use, the most commonly-used dietary supplements were vitamin/mineral supplements in both males and females, then protein and weight loss supplements in males and females, respectively. Although most students obtained information about dietary supplements via the Internet, they typically purchased the supplements from drug stores. Of the students surveyed, 7.5% who were currently using or used to use dietary supplements experienced adverse effects, with no significant difference between genders (8.8% in male, 7.0% in female). In conclusion, the prevalence of dietary supplement use increased with grade among college students in Japan. Some of them experienced adverse effects. Education may be important to prevent adverse effects resulting from supplement use in college.

AIM Resveratrol has been shown to mimic the beneficial effects of dietary restriction (DR). We previously reported that DR delays stroke onset and extends the lifespan in Stroke-Prone Spontaneously Hypertensive rats (SHRSP). Therefore, we examined whether resveratrol mimics DR and delays stroke onset in SHRSP. METHODS Cerebrovascular endothelial cells (CVECs) from SHRSP were treated with resveratrol, and the inflammatory gene expression levels and NFκB protein levels were measured. In order to address the effects of resveratrol in vivo, SHRSP (male, 10 weeks of age) were fed an experimental diet containing several doses of resveratrol (0 - 0.05% (w/w)), after which we measured the plasma cytokine levels and examined the stroke onset and lifespan. RESULTS Treatment with resveratrol (100 μM, 24 hours) in CVECs from SHRSP significantly decreased the interleukin (IL)-1β-induced monocyte chemoattractant protein-1 (MCP-1) mRNA expression levels and p50 and p65 protein levels in the nuclear fraction. When the SHRSP were fed a diet containing resveratrol for one week, the resveratrol treatment did not affect the plasma lipid and glucose levels, body weight or weight of each tissue. Resveratrol slightly, but not significantly, decreased the plasma levels of IL-1β and MCP-1 compared with that observed in the control group. In addition, resveratrol decreased the IL-1β and MCP-1 mRNA expression levels in the brain versus the control animals. However, no doses of resveratrol delayed stroke onset or extended the lifespan in SHRSP. CONCLUSIONS In this study, resveratrol did not delay stroke onset in SHRSP, although it partially suppressed systemic and cerebral inflammation. These results suggest that resveratrol does not mimic the beneficial effects of DR on stroke in vivo.